Encapsulation of drugs in intact erythrocytes: an intravenous delivery system

A number of drugs and the plasma antiprotease alpha 1-antitrypsin has been encapsulated in intact erythrocytes after hypotonic swelling, using a technique designed to preserve the viability of the cells. By labelling the cells with fluorescein isothiocyanate it has been shown that the cells survive exceptionally well when returned to the animal's circulation. Cell survival has been demonstrated in the rat, rabbit and guinea-pig. With encapsulation of cortisol-21-phosphate and methotrexate it was found that blood levels of the drug were maintained for a longer period than when the free drug was administered. Cortisol-21-phosphate was hydrolysed enzymatically by acid phosphatase located primarily in the erythrocyte membrane. An in vitro test involving the interaction or erythrocytes with phagocytes was developed to determine the viability or erythrocytes after being subjected to the encapsulation process. Preparations which did not interact with phagocytes survived when returned to the animal's circulation. The encapsulation procedure increased the fragility of the cell membrane compared to that of normal cells as measured by the leakage of haemoglobin after thermal treatment but it was found that encapsulated cortisol-21-phosphate in cells actually stabilized the membrane. The electrical charge on the membrane of encapsulating cells was the same as that of the normal cells. The charge on reformed ghosts was lower than that of normal cells. Reformed ghosts were rapidly removed when introduced into the circulation. The encapsulation procedure and its possible applications are discussed.